Behavioural Functions and Cerebral Blood Flow in a P301S Tauopathy Mouse Model: A Time-Course Study

Tauopathies refer to a group of neurodegenerative diseases with intracellular accumulation of hyperphosphorylated and aggregated microtubule-associated protein tau (MAPT) in neurons and glial cells. PS19 mice bearing the MAPT P301S mutation have been used to mimic human frontotemporal lobar degeneration. The present study was designed to systematically investigate how behavioural functions, resting cerebral blood flow (CBF) and tau pathology change in PS19 mice at 2, 4, 6, 8 and 12 months of age in a single study under one experimental condition, allowing for the cumulative assessment of age- and genotype-dependent changes. PS19 mice displayed hyperactivity and reduced anxiety levels with age, early and persistent spatial working memory deficits and reduced resting neocortical CBF. Immunoblotting and immunohistochemistry revealed age-related increases in phosphorylated tau in the brain of PS19 mice. In conclusion, the present study, for the first time, cumulatively demonstrated the time-course of changes in behavioural functions, resting CBF and tau pathology in a P301S tauopathy mouse model through their developmental span. This information provides further evidence for the utility of this model to study neurodegenerative events associated with tauopathy and tau dysfunction.

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Effect of Transcranial Direct Current Stimulation over the Primary Motor Cortex on Cerebral Blood Flow: A Time Course Study Using Near-infrared Spectroscopy

Advances in Experimental Medicine and Biology - Oxygen Transport to Tissue XXXVII ◽

10.1007/978-1-4939-3023-4_42 ◽

2016 ◽

pp. 335-341 ◽

Cited By ~ 9

Author(s):

Haruna Takai ◽

Atsuhiro Tsubaki ◽

Kazuhiro Sugawara ◽

Shota Miyaguchi ◽

Keiichi Oyanagi ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Infrared Spectroscopy ◽

Motor Cortex ◽

Near Infrared Spectroscopy ◽

Direct Current ◽

Time Course ◽

Near Infrared ◽

Primary Motor Cortex ◽

Time Course Study

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Blood-brain barrier permeability of 11C-labeled alcohols and 15O-labeled water

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1976.230.2.543 ◽

1976 ◽

Vol 230 (2) ◽

pp. 543-552 ◽

Cited By ~ 217

Author(s):

ME Raichle ◽

JO Eichling ◽

MG Straatmann ◽

MJ Welch ◽

KB Larson ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Time Course ◽

Brain Capillary ◽

Permeability Characteristics ◽

Permeability Surface ◽

Brain Barrier Permeability ◽

The Individual ◽

The Brain

The extraction of 11C-labeled methanol, ethanol, and isopropanol, as well as 15O-labeled water by the brain during a single capillary transit, was studied in vivo in six adult rhesus monkeys by external detection of the time course of these tracers subsequent to their internal carotid artery injection. The data demonstrate the feasibility of accurately measuring brain permeability of highly diffusible substances by this technique and show that neither water nor the alcohols studied freely equilibrate with brain when the cerebral blood flow exceeds 30 ml/100 g min-1. At a cerebral blood flow of 50 ml/100 g min-1 only about 93% of an injected bolus of labeled water freely exchanges with brain, compared with methanol (93%), ethanol (97%), and isopropanol (99%). The brain capillary permeability-surface area (PS) products computed from these data were 0.023 cm3/s g-1 (water), 0.024 cm3/s g-1 (methanol), 0.030 cm3/s g-1 (ethanol), and 0.062 cm3/s g-1 (isopropanol). This sequence of PS products is consistent with the individual lipid solubilities of the alcohols studied and underscores the unique brain permeability characteristics of lipid-insoluble water.

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Measurement of Local Cerebral Blood Flow with [14C]Iodoantipyrine in the Mouse

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1988.16 ◽

1988 ◽

Vol 8 (1) ◽

pp. 121-129 ◽

Cited By ~ 106

Author(s):

Therese M. Jay ◽

Giovanni Lucignani ◽

Alison M. Crane ◽

Jane Jehle ◽

Louis Sokoloff

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Time Course ◽

Local Cerebral Blood Flow ◽

Sources Of Error ◽

Arterial Blood ◽

Appropriate Care ◽

Rapid Removal ◽

The Brain

Local cerebral blood flow was measured in the mouse by means of the [14C]iodoantipyrine method. This method has been previously used in the monkey, dog, cat, and rat, but its application to small mammals such as the mouse requires special attention to potential sources of error. The small size of the mouse brain requires special attention to the rapid removal and freezing of the brain to minimize effects of postmortem diffusion of tracer in the tissue. Because of the relatively low diameter/length ratios of the catheters needed for arterial sampling in small animals, substantial errors can occur in the determination of the time course of the [14C]iodoantipyrine concentration in the arterial blood unless corrections for lag time and dead space washout in the catheter are properly applied. Local cerebral blood flow was measured in seven awake mice with appropriate care to minimize these sources of error. The values were found to vary from 48 ml/100 g/min in the corpus callosum to 198 ml/100 g/min in the inferior colliculus. The results demonstrate that the [14C]iodoantipyrine method can be used to measure local cerebral blood flow in the mouse and that the values in that species are, in general, somewhat higher than those in the rat.

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Time Course of Anoxia-Induced Increase in Cerebral Blood Flow Rate in Turtles: Evidence for a Role of Adenosine

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1994.110 ◽

1994 ◽

Vol 14 (5) ◽

pp. 877-881 ◽

Cited By ~ 41

Author(s):

Patrick Hylland ◽

Göran E. Nilsson ◽

Peter L. Lutz

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Flow Rate ◽

Time Course ◽

Blood Flow Rate ◽

Fold Increase ◽

Systemic Blood Pressure ◽

The Brain ◽

Survival Mechanisms

The exceptional ability of the turtle brain to survive prolonged anoxia makes it a unique model for studying anoxic survival mechanisms. We have used epiillumination microscopy to record blood flow rate in venules on the cortical surface of turtles ( Trachemys scripta). During anoxia, blood flow rate increased 1.7 times after 45–75 min, whereupon it fell back, reaching preanoxic values after 115 min of anoxia. Topical super-fusion with adenosine (50 μ M) during normoxia caused a 3.8-fold increase in flow rate. Superfusing the brain with the adenosine receptor blocker aminophylline (250 μ M) totally inhibited the effects of both adenosine and anoxia, while aminophylline had no effect on normoxic flow rate. None of the treatments affected systemic blood pressure. These results indicate an initial adenosine-mediated increase in cerebral blood flow rate during anoxia, probably representing an emergency response before deep metabolic depression sets in.

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Brain and Blood Concentrations of Propofol after Rapid Intravenous Injection in Sheep, and Their Relationships to Cerebral Effects

Anaesthesia and Intensive Care ◽

10.1177/0310057x9602400406 ◽

1996 ◽

Vol 24 (4) ◽

pp. 445-452 ◽

Cited By ~ 32

Author(s):

G. L. Ludbrook ◽

R. N. Upton ◽

C. Grant ◽

E. C. Gray

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Intravenous Injection ◽

Time Course ◽

Pharmacokinetic Analysis ◽

Depth Of Anaesthesia ◽

Blood Concentrations ◽

Arterial Blood ◽

Close Relationship ◽

The Brain

The time-course of propofol concentrations in the blood and brain following rapid administration of three doses were examined using a sheep preparation and regional pharmacokinetic techniques. These were compared to the time-course of cerebral effects of propofol reported previously. There were marked differences between the time-course of propofol concentrations in arterial blood and the brain, with a close relationship between the time-course of brain concentrations and effects on depth of anaesthesia and CBF. There was evidence that the effect of propofol on cerebral blood flow altered its own rate of elution from the brain. Hysteresis between arterial propofol concentrations and cerebral effects following rapid IV administration therefore appears to have a pharmacokinetic basis, and conventional compartmental pharmacokinetic analysis using blood concentrations alone may fail to accurately predict the time-course of both brain propofol concentrations and depth of anaesthesia.

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β-Lactolin, a Whey-Derived Gly-Thr-Trp-Tyr Lactopeptide, Promotes Cerebral Blood Flow During Cognitive Tasks: A Randomized Controlled Trial

Current Developments in Nutrition ◽

10.1093/cdn/nzab049_002 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 889-889

Author(s):

Yasuhisa Ano ◽

Keiko Kobayashi ◽

Takashi Koikeda ◽

Ryuta Kawashima

Keyword(s):

Working Memory ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Near Infrared ◽

Spatial Working Memory ◽

Controlled Trial ◽

Statistical Significance ◽

Memory Task ◽

Double Blind Study ◽

Age Related

Abstract Objectives Due to the rapid aging of society, the prevention of age-related cognitive decline and dementia has gained increasing attention. Recent epidemiological investigations have shown that the consumption of dairy products reduces the risk of dementia in older adults. β-lactolin, a whey-derived Gly-Thr-Trp-Tyr lactopeptide, activates the dopaminergic system, improves memory impairment, and prevents Alzheimer's pathologies in a rodent model. We have demonstrated that β-lactolin supplementation improves memory retrieval and selective attention in randomized trials. On the other hand, the mechanisms underlying the effects of β-lactolin on human brain activity have not been investigated. Methods We examined the effects of β-lactolin on cerebral blood flow (CBF) using near-infrared spectroscopy (NIRS) in a placebo-controlled randomized double-blind study. Fifty healthy participants (45–60 years old) were randomly allocated to the β-lactolin and placebo groups and supplemented for 6 weeks. At 0 and 6 weeks of the intervention, oxyhemoglobin (Hb) was measured using 34-channel (CH) NIRS during the working memory tasks. Results The changes in oxy-Hb in CH23 located at the left dorsolateral prefrontal cortex (DLPFC) during the spatial working memory task showed a higher statistical significance (false discovery rate (q) = 0.045) in the β-lactolin than in the placebo group. The CBF changes in CH23 were correlated with the reaction time for the working memory task. A recent trial using a 2-CH NIRS also showed a significant CBF increase in the DLPFC area after β-lactolin supplementation. Conclusions β-lactolin supplementation increases CBF in the DLPFC area, which contributes to improved cognitive functions. Funding Sources Current study was funded by Kirin Holdings Co. Ltd.

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Associations between Total Cerebral Blood Flow and Age Related Changes of the Brain

PLoS ONE ◽

10.1371/journal.pone.0009825 ◽

2010 ◽

Vol 5 (3) ◽

pp. e9825 ◽

Cited By ~ 23

Author(s):

Adriaan C. G. M. van Es ◽

Jeroen van der Grond ◽

V. Hester ten Dam ◽

Anton J. M. de Craen ◽

Gerard J. Blauw ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Age Related ◽

The Brain ◽

Age Related Changes

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Patterns of Cerebral Blood Flow and Systemic Hemodynamics During Arithmetic Processing

Journal of Psychophysiology ◽

10.1027/0269-8803.22.2.81 ◽

2008 ◽

Vol 22 (2) ◽

pp. 81-90 ◽

Cited By ~ 21

Author(s):

Natalie Werner ◽

Neval Kapan ◽

Gustavo A. Reyes del Paso

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Time Course ◽

Doppler Sonography ◽

Transcranial Doppler Sonography ◽

Systemic Hemodynamics ◽

Heart Period ◽

Blood Flow Velocities ◽

Flow Velocities

The present study explored modulations in cerebral blood flow and systemic hemodynamics during the execution of a mental calculation task in 41 healthy subjects. Time course and lateralization of blood flow velocities in the medial cerebral arteries of both hemispheres were assessed using functional transcranial Doppler sonography. Indices of systemic hemodynamics were obtained using continuous blood pressure recordings. Doppler sonography revealed a biphasic left dominant rise in cerebral blood flow velocities during task execution. Systemic blood pressure increased, whereas heart period, heart period variability, and baroreflex sensitivity declined. Blood pressure and heart period proved predictive of the magnitude of the cerebral blood flow response, particularly of its initial component. Various physiological mechanisms may be assumed to be involved in cardiovascular adjustment to cognitive demands. While specific contributions of the sympathetic and parasympathetic systems may account for the observed pattern of systemic hemodynamics, flow metabolism coupling, fast neurogenic vasodilation, and cerebral autoregulation may be involved in mediating cerebral blood flow modulations. Furthermore, during conditions of high cardiovascular reactivity, systemic hemodynamic changes exert a marked influence on cerebral blood perfusion.

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Vorläufige Ergebnisse von 99mTc-HMPAO-SPECT-Untersuchungen bei endogenen Psychosen

Nuklearmedizin ◽

10.1055/s-0038-1629475 ◽

1989 ◽

Vol 28 (03) ◽

pp. 88-91

Author(s):

J. Schröder ◽

H. Henningsen ◽

H. Sauer ◽

P. Georgi ◽

K.-R. Wilhelm

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Regional Cerebral Blood Flow ◽

Regions Of Interest ◽

Post Mortem ◽

Regional Cerebral Blood ◽

Hmpao Spect ◽

Endogenous Psychoses ◽

The Brain ◽

99Mtc Hmpao

18 psychopharmacologically treated patients (7 schizophrenics, 5 schizoaffectives, 6 depressives) were studied using 99mTc-HMPAO-SPECT of the brain. The regional cerebral blood flow was measured in three transversal sections (infra-/supraventricular, ventricular) within 6 regions of interest (ROI) respectively (one frontal, one parietal and one occipital in each hemisphere). Corresponding ROIs of the same section in each hemisphere were compared. In the schizophrenics there was a significantly reduced perfusion in the left frontal region of the infraventricular and ventricular section (p < 0.02) compared with the data of the depressives. The schizoaffectives took an intermediate place. Since the patients were treated with psychopharmaca, the result must be interpreted cautiously. However, our findings seem to be in accordance with post-mortem-, CT- and PET-studies presented in the literature. Our results suggest that 99mTc-HMPAO-SPECT may be helpful in finding cerebral abnormalities in endogenous psychoses.

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